Antibodies to mutated citrullinated vimentin for diagnosing rheumatoid arthritis in anti-CCP-negative patients and for monitoring infliximab therapy

Abstract

IntroductionAntibodies against cyclic citrullinated peptides (CCPs) are useful for diagnosing rheumatoid arthritis (RA). Antibodies to mutated citrullinated vimentin (MCV) were described recently in RA. The aims of this study were to evaluate the usefulness of anti-MCV for diagnosing RA in anti-CCP-negative patients and to monitor anti-MCV titres during infliximab therapy for RA.MethodsWe studied two groups of RA patients, one with (n = 80) and one without (n = 76) anti-CCP antibodies. The specificity of anti-MCV was evaluated by investigating 50 healthy controls and 158 patients with other rheumatic diseases (51 psoriatic rheumatism, 58 primary Sjögren syndrome, and 49 ankylosis spondylitis). Serum anti-MCV and anti-CCP titres were measured in 23 patients after 6, 12, 18, and 24 months of infliximab treatment. Anti-CCP2 and anti-MCV levels were assayed using a commercial enzyme-linked immunosorbent assay. IgM rheumatoid factor was determined by nephelometry.ResultsIn accordance with the cutoff values recommended by the manufacturer, the specificity of anti-MCV antibodies was 90.9%. We adjusted the cutoff values to obtain the same specificity as that of anti-CCP antibodies (94.2%). With this optimal cutoff, anti-MCV antibodies were found in 11.8% (9/76) of RA patients without anti-CCP, and similarly, anti-CCP antibodies were found in 11.2% (9/80) of RA patients without anti-MCV. Anti-MCV antibodies were positive in 6 patients who tested negative for both anti-CCP and rheumatoid factor. Anti-MCV titres were significantly decreased after 18 and 24 months of infliximab therapy compared with baseline (P < 0.01) as a significant decrease of anti-CCP levels occurred only at 24 months (P < 0.04). Moreover, an anti-MCV decrease was significantly associated with DAS28 (disease activity score using 28 joint counts) improvements 12 months into therapy.ConclusionsOur results suggest that anti-MCV antibodies may be valuable for diagnosing RA in anti-CCP-negative patients without replacing them as an equivalent number of anti-CCP-positive RA patients test negative for anti-MCV. Moreover, anti-MCV antibodies could be useful for monitoring the effects of infliximab therapy.

Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

“…The prevalence among our study group was therefore comparable to that among 89 previously published series [26]. The titre of the a-MCV antibodies showed a significant correlation with the titre of a-CCP (R=0.83, p<0.0001) and that of total RF (R=0.46, p=0.0007) and RF IgA (R=0.…”

“…The reduction in RF IgA serum levels is less significant at month +1 ( 4 p) than at month +3 ( 5 p) and month +6 ( 6 p) RF, rheumatoid factor Table 3 Changes in serum levels of autoantibodies during the follow-up after RTX treatment in relation to the response according to the EULAR criteria at month +6 EULAR response Baseline Month +3 Month +6 value [44,45]. But in some early studies a-MCV appeared more sensitive than a-CCP antibodies, although less specific [26,46,47]. However, more recent metaanalyses [28,29] have shown a total overlapping diagnostic power between a-CCP and a-MCV testing, leading to the proposal of a-MCV analysis as a second-level test in selected cases of patients with a strongly suspected diagnosis of RA and who are negative for both a-CCP and RF.…”

“…Numerous studies have been formalized using experimental and commercial tests for a-MCV. These studies have shown that the sensitivity of a-MCV antibodies is similar to that of a-CCP, and the specificity is slightly lower [26][27][28][29]. The predictive power in relation to radiographic progression and a high association with the shared epitope are even higher for a-MCV than for a-CCP antibodies [30,31], but for a-MCV major prognostic information is linked to a high titre and not to its mere presence [31].…”

“…It cannot replace a-CCP, but they can certainly occur together, because a small percentage of patients with RA are a-MCV-positive and a-CCP negative. Thus a-MCV antibodies could be used as second level test to support the diagnosis of RA in patients with a strong suspicion who are negative for a-CCP and RF [26].…”

“…Recently, the a-MCV antibodies have been investigated in the follow-up of patients with RA treated with anti-TNF-α/drugs, and they appear to have added value compared to the classic assay of a-CCP and RF since a-MCV antibodies decrease more quickly and are associated with clinical improvement [26]. Nothing has yet been reported for treatment with RTX, a drug that is directed to the autoantibody secreting cells.…”